GPT-based chatbot tools are still unreliable in the management of prosthetic joint infections.

BACKGROUND: Artificial intelligence chatbot tools responses might discern patterns and correlations that may elude human observation, leading to more accurate and timely interventions. However, their reliability to answer healthcare-related questions is still debated. This study aimed to assess the performance of the three versions of GPT-based chatbots about prosthetic joint infections (PJI). METHODS: Thirty questions concerning the diagnosis and treatment of hip and knee PJIs, stratified by a priori established difficulty, were generated by a team of experts, and administered to ChatGPT 3.5, BingChat, and ChatGPT 4.0. Responses were rated by three orthopedic surgeons and two infectious diseases physicians using a five-point Likert-like scale with numerical values to quantify the quality of responses. Inter-rater reliability was assessed by interclass correlation statistics. RESULTS: Responses averaged "good-to-very good" for all chatbots examined, both in diagnosis and treatment, with no significant differences according to the difficulty of the questions. However, BingChat ratings were significantly lower in the treatment setting (p = 0.025), particularly in terms of accuracy (p = 0.02) and completeness (p = 0.004). Agreement in ratings among examiners appeared to be very poor. CONCLUSIONS: On average, the quality of responses is rated positively by experts, but with ratings that frequently may vary widely. This currently suggests that AI chatbot tools are still unreliable in the management of PJI.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Induced membrane technique using enriched bone grafts for treatment of posttraumatic segmental long bone defects.

BACKGROUND: Reconstruction of posttraumatic bone defects represents a difficult challenge. The induced membrane technique is an effective two-stage procedure for bone defect reconstruction. To overcome the problems of autologous bone grafting, different graft substitutes have been investigated. The aim of the present study is to evaluate our clinical experience in reconstruction of critical posttraumatic bone defects using an induced membrane technique based on a combination of autologous graft and allograft (cancellous bone) enriched with platelet-rich plasma (PRP) and bone marrow concentrate aspirate (BMCA). MATERIALS AND METHODS: Between 2009 and 2014, we reconstructed 18 posttraumatic bone defects in 16 patients. Their average length was 6.4 cm (range 1.6-13.2 cm). The defect location was the femur in nine cases (50%), the tibia in eight (44%) cases, and the humerus in one (6%) case. In all cases, we used a combination of autologous and cancellous allograft graft enriched with PRP and BMCA. Bone fixation was achieved using intramedullary nailing in 2 cases (11%), plating in 15 cases (66%), and external fixation in 1 case (6%). RESULTS: Both clinical and radiographic union were achieved in 13 (72%) cases (13 patients). Five (28%) cases (four patients) developed nonunion. Nonunion was observed in two of eight (25%) tibial defects and in three (33%) of nine femoral defects (ns). Three of 4 (75%) double defects had delayed union, whereas 2 of 14 (14%) single defects did not heal (p = 0.016). The average length of the 13 defects that united was 6 cm (range 1.6-11.8 cm), while the length of the 5 defects that did not unite was 10.3 cm (range 6-13.2 cm) (p = 0.009). CONCLUSIONS: In this series using an induced membrane technique based on a combination of autograft and allograft enriched with BMCA and PRP, the healing rate was lower than in other series where autologous bone graft alone was employed. Nonunion was more frequent in longer and double defects. Further research aimed at developing effective alternative options to autogenous cancellous bone graft is desirable. LEVEL OF EVIDENCE: III.

Intercalary reconstruction of femur after tumour resection: is a vascularized fibular autograft plus allograft a long-lasting solution?

Aims: After intercalary resection of a bone tumour from the femur, reconstruction with a vascularized fibular graft (VFG) and massive allograft is considered a reliable method of treatment. However, little is known about the long-term outcome of this procedure. The aims of this study were to determine whether the morbidity of this procedure was comparable to that of other reconstructive techniques, if it was possible to achieve a satisfactory functional result, and whether biological reconstruction with a VFG and massive allograft could achieve a durable, long-lasting reconstruction. Patients and Methods: A total of 23 patients with a mean age of 16 years (five to 40) who had undergone resection of an intercalary bone tumour of the femur and reconstruction with a VFG and allograft were reviewed clinically and radiologically. The mean follow-up was 141 months (24 to 313). The mean length of the fibular graft was 18 cm (12 to 29). Full weight-bearing without a brace was allowed after a mean of 13 months (seven to 26). Results: At final follow-up, the mean Musculoskeletal Tumor Society Score of 22 evaluable patients was 94% (73 to 100). Eight major complications, five fractures (21.7%), and three nonunions (13%) were seen in seven patients (30.4%). Revision-free survival was 72.3% at five, ten, and 15 years, with fracture and nonunion needing surgery as failure endpoints. Overall survival, with removal of allograft or amputation as failure endpoints, was 94.4% at five, ten, and 15 years. Discussion: There were no complications needing surgical revision after five years had elapsed from surgery, suggesting that the mechanical strength of the implant improves with time, thereby decreasing the risk of complications. In young patients with an intercalary bone tumour of the femur, combining a VFG and massive allograft may result in a reconstruction that lasts a lifetime. Cite this article: Bone Joint J 2018;100-B:378-86.

Cryotherapy efficacy and safety as local therapy in surgical treatment of musculoskeletal tumours. A retrospective case series of 143 patients.

Cryotherapy, also called Cryoablation (CA), is a technique that provides a local treatment to various pathological conditions. In Musculoskeletal tumours management, Cryoablation is well accepted and validated as a treatment in palliative cures for metastatic patients. Recently, CA has been proposed also as an alternative to radiofrequency ablation in osteoid osteoma and other benign tumour treatment with promising results. Cryotherapy with argon ice-balls as local adjuvant in open surgery is a tool that can provide enlargement of surgical margins if used properly. There is still not enough evidence supporting use of cryotherapy as local adjuvant in Musculoskeletal open surgery as the series cited above are very small and there is no comparative RCT between local adjuvant therapies including CA. One-hundred-and-eighty-three patients were treated with Cryoablation from 2000 and 2018 in the Musculoskeletal Tumours Surgery Unit of Careggi (Florence) and the University 2nd Clinic of Pisa. In our study group, 38 patients (26.6%) were affected by bone metastasis, 16 patients (11.1%) by aneurismal bone cysts or angiomas, 22 patients (15.4%) by low-grade malignant musculoskeletal tumours, 2 patients (1,4%) by fibromatosis, 63 patients (44.1%) by benign musculoskeletal tumours (principally Giant Cell Tumours-GCT) and 2 patients (1.4%) by Osteosarcomas. In 125 cases (87.4%), CA has been used as an adjuvant therapy, in 12 cases (8.4%) as a percutaneous ablation therapy and in 6 cases (4.2%) as adjuvant to remove tumoral lesions 'en bloc' or as a 'poor technique' for its sterilizing effect on previously resected bones. Mean follow-up was 10 years. Twenty-three patients (16%) were classified as Alive with Disease (AWD) due to local recurrence or tumour progression (14 metastases, 5 low-grade malignant bone tumours, 4 Giant Cell Tumours). Eight patients died due to the disease (6 metastases, 2 osteosarcomas), while 1 died from leukaemia. One-hundred-and-eleven patients (78%) were classified as Continues Disease Free (CDF). All patients reported decrease in pain-related symptoms after surgery and all surgeons reported better control of blood loss. Three cases (2%) of local skin necrosis or wound dehiscence were reported. No local recurrences were reported after fibromatosis ablation. Our results confirm that CA could be considered as a safe and effective technique to treat various conditions as adjuvant and palliative therapy. In particular, in open surgery, cryotherapy as an adjuvant treatment could lead to very low rates of recurrence in locally aggressive tumours like Giant Cell Tumours. These results could be generalized but a better understanding about indications and outcomes can be reached studying CA in specific populations with comparation to other adjuvant techniques.

Complications and survival of megaprostheses after resection of bone metastases.

Treatment of bone metastases is often palliative, aiming at pain control and stabilization or prevention of pathological fractures. However, a complete resection with healing purposes can be performed in selected cases. The aim of our work was to evaluate the survival of megaprostheses used for reconstruction after bone metastases. Between January 2001 and March 2015, we implanted 169 Megasystem-C® (Waldemar LINK® GmbH & Co. KG, Hamburg, Germany) after bone metastasis resection. Patients, 95 females and 74 males, were operated at an average age of 61 (12-87) years for proximal femoral resection in 135 (79.9%) cases, distal femur in 24 (14.2%), proximal tibia in 6 (3.6%), total femur in 3 (1.8%) and intercalary femur in 1 (0.6%). Mostly, breast cancer metastases (30.8%), kidney (17.8%) and lung (14.2%) were treated. At an average follow-up of 21 (1-150) months, we found a 99.4% overall limb salvage and a 96.1% overall survival rate at 1 year, 92.8% at 2 years, and 86.8% at 5 and 10 years. We found 9 (5.3%) mobilization cases of the proximal femoral implant, 3 needed surgical reduction; 2 (1.2%) cases of aseptic loosening of the prosthetic stem; 2 (1.2%) periprotetic infection cases, one requiring a 2-stage revision. Few literature studies have evaluated the survival of megaprosthetic implant in the treatment of bone metastases. Our data show how in this specific context the rate of complications is significantly lower than expected in general orthopedic orthopedic surgery. The use of modular prostheses is a valid reconstructive strategy after bone metastasis resection in selected patients. The rate of short-term complications is exceptionally low; further studies will have to confirm this in the longer term.

OSTEOARTICULAR ALLOGRAFTS IN PAEDIATRIC BONE TUMOR RECONSTRUCTION OF THE KNEE.

Osteoarticular allografts represent a reconstructive option after bone tumor resection around the knee in growing children. The major advantage is the chance to preserve the growth plate of the remaining bone, but the disadvantage is the high failure rate eventually requiring definitive prosthetic replacement at skeletal maturity. We retrospectively reviewed 22 patients who underwent osteoarticular allograft reconstructions of the distal femur (16) or proximal tibia (6). There were 12 females and 10 males with an average age at surgery of 11 years (7-15). The diagnosis was osteosarcoma in 19 cases and Ewing sarcoma in 3. All patients underwent pre- and post-operative chemotherapy. At an average follow-up of 103 months (12-167), 18 patients (82%) were alive and 4 had died (18%). We observed 10 allograft failures requiring prosthetic replacement, 6 in distal femur and 4 in proximal tibia reconstructions. At last follow-up 8 allografts (36%) were still in place. Overall allograft survival was 79.6% at five and 45.8% at ten years. In distal femur, allograft survival was 86.2% at five and 59.1% at ten years. In proximal tibia, allograft survival was 62.5% at 5 years and 31.2% at 67 months. Average limb shortening was 3 cm (0- 5) in 8 patients with the allograft still in situ and 2 cm (0-4) in 10 patients after prosthetic replacement. Average MSTS functional score of the whole series was 25 (83.7%). The MSTS score of patients after revision with prosthetic replacement was 24 (80%) while patients who still had the allograft retained had an average MSTS scores of 26.8 (89.3%). In conclusion, osteoarticular allograft reconstruction of the knee after bone tumor resection in pediatric age can be considered a temporary solution with the aim to limit limb length discrepancy before definitive prosthetic replacement after skeletal maturity.

Giant cell tumours of the small bones of the hands and feet: long-term results of 30 patients and a systematic literature review.

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation. We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome. At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet.

Scaffolds combined with stem cells and growth factors in healing of pseudotumoral lesions of bone.

Reconstructions of large lesions or defects often require a bone graft or a bone substitute to promote healing. In common practice the reconstruction of a bone defect is dependent on the site and size of the lesion: in long bones intercalary defects may be managed with Ilizarov technique of bone transport and distraction osteogenesis or the use of a free or pedicled vascularized bone graft, or with Masquelet technique. For cavitary defects the available surgical options include autograft, allograft or xenograft or the use of synthetic scaffolds to promote bone regeneration. In order to promote a faster bone healing tissue engineering proposed the application of enriched graft to fill bone defects. The employment of enriched bone graft has been our choice in the last years to fill contained defects following curettage of a pseudotumoral lesion of bone. We report our clinical experience in terms of safety and success of these procedures at a long-term follow up.

The use of osteo-articular allografts for reconstruction after resection of the distal radius for tumour.

Several techniques have been described to reconstruct a mobile wrist joint after resection of the distal radius for tumour. We reviewed our experience of using an osteo-articular allograft to do this in 17 patients with a mean follow-up of 58.9 months (28 to 119). The mean range of movement at the wrist was 56° flexion, 58° extension, 84° supination and 80° pronation. The mean ISOLS-MSTS score was 86% (63% to 97%) and the mean patient-rated wrist evaluation score was 16.5 (3 to 34). There was no local recurrence or distant metastases. The procedure failed in one patient with a fracture of the graft and an arthrodesis was finally required. Union was achieved at the host-graft interface in all except two cases. No patient reported more than modest non-disabling pain and six reported no pain at all. Radiographs showed early degenerative changes at the radiocarpal joint in every patient. A functional pain-free wrist can be restored with an osteo-articular allograft after resection of the distal radius for bone tumour, thereby avoiding the donor site morbidity associated with an autograft. These results may deteriorate with time.

Biological reconstruction after resection of bone tumours around the knee: long-term follow-up.

We reviewed 25 patients who had undergone resection of a primary bone sarcoma which extended to within 5 cm of the knee with reconstruction by a combination of a free vascularised fibular graft and a massive allograft bone shell. The distal femur was affected in four patients and the proximal tibia in 21. Their mean age at the time of operation was 19.7 years (5 to 52) and the mean follow-up period 140 months (28 to 213). Three vascularised transfers failed. The mean time to union of the fibula was 5.6 months (3 to 10) and of the allograft 19.6 months (10 to 34). Full weight-bearing was allowed at a mean of 21.4 months (14 to 36). The mean functional score at final follow-up was 27.4 (18 to 30) using a modified 30-point Musculoskeletal Tumour Society rating system. The overall limb-salvage rate was 88%. The results of our study suggest that the combined use of a vascularised fibular graft and allograft is of value as a limb-salvage procedure for intercalary reconstruction after resection of bone tumours around the knee, especially in skeletally immature patients.

A novel recessive mutation of fibroblast growth factor-23 in tumoral calcinosis.

BACKGROUND: Tumoral calcinosis is a rare disease characterized by hyperphosphatemia due to hypophosphaturia and by ectopic calcifications. Phosphatonins are important hormones that regulate phosphorus homeostasis. Tumoral calcinosis is a rare congenital disorder in which the differential diagnosis from other syndromes associated with extraskeletal calcifications may be difficult. Mutations in the UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-3 (GALNT3) and fibroblast growth factor-23 (FGF23) genes have been described. Mutational analysis is important for the early recognition of the disorder, for prevention of its complications, and for family screening strategies. We examined two unrelated white patients affected by tumoral calcinosis. METHODS: The first patient was a woman with a history of an ectopic calcification in the left shoulder. The second patient was a man with a history of an ectopic calcification in the right buttock. Routine biochemistry and FGF-23 assays were performed on serum samples. Genomic DNA was extracted from peripheral blood. The FGF23 and GALNT3 genes were analyzed by direct sequencing. RESULTS: A new homozygous H41Q codon 41, C-->A transversion at position 123 (c.123C>A) in exon 1 of the FGF23 gene was evidenced in both patients. No mutation of the GALNT3 gene was detected in these patients. As determined by an ELISA assay, intact FGF-23 circulating protein was low in both patients. CONCLUSIONS: This is the fourth mutation of the FGF23 gene described in subjects with tumoral calcinosis.

Limb salvage surgery in combination with brachytherapy and external beam radiation for high-grade soft tissue sarcomas.

While combined treatment of high-grade soft tissue sarcoma with resection and radiotherapy has become an accepted standard, outlines of treatment algorithms remain a matter of debate. Our institutional practice foresees wide surgical resection with adjuvant brachytherapy and external beam radiation. It was the purpose of this study to determine long-term outcome, prognostic factors for local and systemic recurrence and morbidity in patients with high-grade soft tissue sarcomas of the extremities, who were subjected to this regimen. One hundred and twelve patients met the inclusion criteria (56 male, 56 female; median age, 50 years). Median follow-up was 75 months (min. 11 months). Overall survival rate was 77.5% and 71.1% at 5 and 7 years, respectively. Disease-free survival rate was 63.3% and 58.4% at 5 and 10 years, respectively. Local control was achieved in 91.5% and 87.0% at 5 and 10 years, respectively. Wide surgical margins were associated with a significantly better local control rate compared to marginal or intralesional margins. Tumor size did correlate with systemic but not local recurrence. Tumor site and histotype did not appear to have an impact on outcome. Chemotherapy did not show to have an impact on local or systemic control. Fourteen patients (12.5%) had local complications attributed to radiotherapy. Eleven patients developed wound-healing problems, which needed further surgery. Using our treatment algorithm for high-grade soft tissue sarcoma of the extremities, good local and systemic control can be achieved with a low complication rate.

Soft tissue sarcomas of the popliteal fossa: outcome and risk factors.

BACKGROUND: Limb salvage surgery of popliteal soft tissue sarcomas may be hampered due to the incomplete anatomical containment of this region and the vicinity of neurovascular structures. The scope of this study was to determine outcome and to define risk factors. PATIENTS AND METHODS: 27 patients (53.3+/-15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27 patients were included after prior treatment elsewhere (5 after intralesional resections and 4 local recurrences). The lesions were staged IB in 8/27 patients, IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27 patients. 15/27 patients were subjected to radiation therapy (preoperative in 6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively). RESULTS: Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local recurrence occurred in 2 patients. 8/27 patients developed metastatic disease after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113) did not differ in patients after amputations vs limb salvage. Application of radiation therapy was associated with a better survival (p=0.003). Complications related to the surgical intervention were recorded in 2/27 patients, complications related to radiation therapy occurred in 6/15 patients. DISCUSSION: Despite being extra-compartmental, popliteal sarcomas can be treated with a high rate of limb salvage while equal safety compared to amputations is maintained. Irradiation improved survival in our patient population. In cases with involvement of neurovascular structures, preoperative down-staging with radio or chemo-therapy may prevent amputation.

Osteoid osteoma of the femur with a double nidus: a case report.

Osteoid osteoma is a common benign lesion, that occurs in children and young adults. The authors report the observation of a multifocal lesion which is infrequently reported in the literature. S.A., a 10-year-old female came to our observation complaining of spontaneous pain in her right hip and cruralgia radiating to the homolateral knee over the last 6 months; the symptoms, which increased during the night, were relieved by treatment with NSAIDS. Clinical examination and imaging studies confirmed a diagnosis of osteoid osteoma with a double nidus; the lesion was treated by CT-guided thermo-ablation with radiofrequency under general anaesthesia. Complete regression of symptoms was observed at 2-year follow-up.

Retrieved human allografts : a clinicopathological study.

BACKGROUND: We studied seventy-three massive preserved human allografts, retrieved from two to 156 months after implantation, to provide insight into the mechanisms of their repair. METHODS: The specimens were studied with radiographic and histological techniques that permitted time-related quantitative analysis of the reparative mechanisms of union, cortical repair, soft-tissue attachment, fracture, and characteristics of the allograft-cement interface and the articular cartilage. RESULTS: Union at cortical-cortical junctions occurred slowly (approximately twelve months) by host-derived external callus that bridged the junction and filled the gap between abutting cortices. The bone in the gap did not undergo stress-oriented remodeling even after many years, and, when the union was intentionally disrupted, failure occurred at the cement line that marked the allograft-host junction. Repair of the necrotic graft matrix was both external and internal. External repair consisted of the apposition of a thin seam of host bone on the outer surface of the graft, coating about 40% of the surface at one year and 80% at two years. Internal repair was confined to the ends and the periphery of the cortices and penetrated so slowly that only 15% to 20% of the graft was repaired by five years, after which deeper repair seldom occurred. Graft fractures in specimens retrieved soon after fracture showed only necrotic bone adjacent to the fracture site, whereas those retrieved after fracture-healing showed a marked increase in internal repair of the bone about the fracture site. When bone cement had been used to fix a prosthesis, there was no evidence of bone resorption or loosening of the device. The osteoarticular specimens showed no survival of chondrocytes in the articular cartilage. However, the architecture of the acellular cartilage was well preserved after two to three years and occasionally after as many as five years. Late degenerative changes in the articular cartilage coincided with subchondral revascularization and fragmentation, and the articulating surfaces became covered by a pannus of fibrovascular reparative tissue. Degenerative changes in articular cartilage occurred earlier and were more advanced in specimens retrieved from patients with an unstable joint than in those retrieved from patients with a stable joint. CONCLUSIONS: Repair of massive human allografts is an indolent process that follows a fairly predictable course during the first few years and is influenced by other biological activities, such as fracture repair, supplementary autografting, and tumor recurrence.

Bizarre parosteal osteochondromatous proliferation (Nora's lesion). Description of six cases and a review of the literature.

The authors report their experience with 6 cases of bizarre parosteal osteochondromatous proliferation (BPOP) observed in 4 patients in its typical site (distal ends of the limbs), and in 2 patients where it was instead atypically localized in the humerus and femur. The histories of the patients revealed that 50% reported previous trauma in the site of lesion. Five patients were submitted to surgical exeresis, while the remaining patient refused to undergo any type of treatment because he was asymptomatic. At a mean follow-up of 36 months 1 patient presented with recurrence (20%). BPOP is a rare pseudotumorous lesion with typical radiographic and histopathologic findings similar to to those of other benign and malignant tumor forms. A review of the small amount of literature in existence is used to analyze the elements that may lead to accurate differential diagnosis.

Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high-grade osteosarcomas.

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor beta (TGF beta) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGF beta isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent), while low expression was detected in only three cases (17.7 per cent). For TGF beta 2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF beta 1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGF beta 1 was demonstrated in a few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p = 0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF beta 1 detected by in situ hybridization were significantly higher (p = 0.04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGF beta 1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas.

Synovial chondromatosis in a lumbar apophyseal joint.

A 31-year-old woman presented with painful swelling in the right paravertebral region that had been present for 2 years. Radiography and CT revealed an area of increased density due to multiple calcifications localized at the fourth lumbar vertebra. Histological examination revealed that the lesion consisted of nodules of hyaline cartilage, with focal areas of calcification, growing within synovial tissue.